Peripheral fatigue

Bigland-Ritchie, B., Jones, D.A., Hosking, G.P., Edwards, R.H.T. (1978). Central and peripheral fatigue in sustained maximum voluntary contractions of human quardriceps muscle. Clin. Sci. Mol. Med. 54, 609-614. 

Bigland-Ritchie, B., Bellemare, F., Woods, J.J. (1983a). Central and peripheral fatigue in intermittent submaximal contractions. Neurosci. Abst. 9, 631 (Abstract). 

MJ - the highest level that has ever been reported. It is Peripheral fatigue about seven times the resting energy expenditure of normal adult males (see Table 2.4). 

Although fatigue is common and everyone knows what it is, it is difficult to define. One definition is the inability to maintain the required power output . Fatigue can be divided into two classes, peripheral and central. Peripheral fatigue arises within the muscle whereas central fatigue arises within the brain or the motor nerves. Although fatigue affects most people at some time in their life, there is no acceptable biochemical mechanism(s) to explain it. There are, however, several hypotheses. 

On the basis of the proposed mechanisms for peripheral fatigue and for central fatigue, it is possible to combine the mechanisms to provide an overall summary of all the... 

Figure 13.30 A summaiy diagram illustrating the mechanisms by which central and peripheral fatigue can cause fatigue. Central fatigue could be caused by changes in concentration of blood glucose, 5-HT or lumaine concn. in presynaptic neurones.

Fatigue accompanies viral infection, sepsis, trauma or major surgery. The cause of this fatigue is not known it may be peripheral, central or both. Studies on biopsy samples of patients with trauma show a reduction in the muscle ATP concentration, which could be responsible for peripheral fatigue, as explained above (Chapter 18 Table 13.3). Central fatigue has been identified in three different clinical conditions, post-polio syndrome, multiple sclerosis and after spinal cord injury, but has not been investigated in other conditions. 

The factor responsible for the pain is not known but the increased concentrations of adenosine and/or potassium ions are considered to be involved. These factors are also considered to be a cause of the pain that occurs in the skeletal muscle during peripheral fatigue (Chapter 13). 

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

Fatigue of muscles is found post-exercise and in some patients with disorders of limb or respiratory muscles. Peripheral muscle fatigue is generally characterized by the changes in force frequency relationships that occur. The process is traditionally divided into a failure of force production at either low or high frequencies of electrical stimulation. 

Hypoperfusion of skeletal muscles leads to fatigue, weakness, and exercise intolerance. Decreased perfusion of the central nervous system (CNS) is related to confusion, hallucinations, insomnia, and lethargy. Peripheral vasoconstriction due to SNS activity causes pallor, cool extremities, and cyanosis of the digits. Tachycardia is also common in these patients and may reflect increased SNS activity. Patients will often exhibit polyuria and nocturia. Polyuria is a result of increased release of natriuretic peptides caused by volume overload. Nocturia occurs due to increased renal perfusion as a consequence of reduced SNS renal vasoconstrictive effects at night. In chronic severe HF, unintentional weight loss can occur which leads to a syndrome of cardiac cachexia. This results from several factors, including loss of appetite, malabsorption due to gastrointestinal edema, elevated metabolic rate, and elevated levels of proinflammatory cytokines. 

Docetaxel Myelosuppression, severe fluid retention Alopecia, fatigue, stomatitis, nausea, vomiting, diarrhea, peripheral neuropathy, nail disorder, skin reactions, hypersensitivity reactions... 

Docetaxel asthenia, peripheral neuropathy, alopecia, cardiovascular Fatigue, nausea, vomiting, skin toxicity, neuropathy, anemia, Mild (on administration days... 

Bortezomib (Velcade) Constipation, decreased appetite, asthenia, fatigue, fever, thrombocytopenia, dose-related, reversible peripheral neuropathy Dose 1.3 mg/m2 IV bolus twice weekly for two weeks week 3 off repeat... 

Arsenic trioxide -believed to induce apoptosis -LFT elevations -renal insufficiency -fatigue -hyperglycemia -skin rash -hypokalemia -peripheral neuropathy -high frequency hearing loss... 

Fluid overload can result in pulmonary congestion and peripheral edema. Nonspecific symptoms may include fatigue, nocturia, hemoptysis, abdominal pain, anorexia, nausea, bloating, ascites, poor appetite, ascites, mental status changes, and weight gain. 

Monitoring for major adverse effects should be undertaken they include headache and dizziness with nitrates fatigue and lassitude with /J-blockers and peripheral edema, constipation, and dizziness with calcium channel antagonists. 

While rDNA techniques offer exciting possibilities, there are many unanswered questions about the potential toxicity that each new product represents. For example, acute clinical toxicities of interferons (IFNs) include flu-like syndrome, fever, chills, malaise, anorexia, fatigue, and headache. Chronic dose-limiting toxicities include neutropenia, thrombocytopenia, impairment of myeloid maturation, reversible dose-related hepatotoxicity, some neurological toxicity (stupor, psychosis, peripheral neuropathy) and gastrointestinal toxicity. Some of these toxicities would be difficult to ascertain in rodents, and, in fact, may be species-specific. 

There is a disease known as beriberi that causes weakness, fatigue, psychosis, gastrointestinal problems, peripheral nerve damage, brain damage, and ultimately death. Many years ago, this disease was particularly prevalent in rice-eating Asian societies that polished their rice. The polishings contain an essential human nutrient... 

Figure 13.26 The motor control pathway for stimulation of voluntary contractions. The motor control pathway begins in the motor cortex in the brain and the sequence continues through the spinal cord to the muscle and the myofibrils. It has two components, central and peripheral. One or both components can be involved in biochemical mechanisms of fatigue (see below).

Excessive central stimulation, usually exhibited as tremors, insomnia and hyperhidrosis, can occur following therapeutic doses of the MAOIs, as can agitation and hypomanic episodes. Peripheral neuropathy, which is largely restricted to the hydrazine type of MAOI, is rare and has been attributed to a drug-induced p)n idoxine deficiency. Such side effects as dizziness and vertigo (presumably associated with hypotension), headache, inhibition of ejaculation (which is often also a problem with the TCAs), fatigue, dry mouth and constipation have also been reported. These side effects appear to be more frequently associated with phenelzine use. They are not associated with any antimuscarinic properties of the drug but presumably arise from the enhanced peripheral sympathetic activity which the MAOIs... 

Disulfiram is used as an adjunct in the management of alcohol dependence. It is contraindicated in patients with a history of cerebrovascular accident, cardiac failure, coronary artery disease, hypertension and psychosis. Side-effects that may be present include initial drowsiness and fatigue, nausea, vomiting, halitosis, reduced libido, psychotic reactions, allergic dermatitis, peripheral neuritis and hepatic cell damage. 

Common side-effects associated with beta-adrenoceptor blockers, such as atenolol, include fatigue, bradycardia, sleep disturbances, and peripheral vasoconstriction leading to coldness of extremities. Water-soluble beta-blockers, such as atenolol, are less likely to cause sleep disturbances and nightmares than lipid-soluble beta-blockers, such as propranolol. 

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